Memantine-Derived Schiff Bases as Transdermal Prodrug Candidates
Ana P Araujo de Oliveira1, Victoria C Romero Colmenares1, Renata Diniz1
1Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.
ACS Omega
|April 22, 2022
Summary
Novel Schiff bases derived from memantine (Me) show increased lipophilicity, enhancing potential for transdermal drug delivery. Compound 3, releasing pyridoxal, is a promising prodrug candidate for neurological disorders like Alzheimer's disease.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Drug Delivery
Background:
- Memantine (Me) is used to treat moderate-to-severe Alzheimer's disease.
- Developing novel prodrugs can improve drug delivery and efficacy.
- Schiff base formation is a common strategy for prodrug design.
Purpose of the Study:
- To synthesize novel memantine-derived Schiff bases.
- To evaluate their physicochemical properties for transdermal delivery.
- To assess their potential as prodrug candidates for neurological disorders.
Main Methods:
- Condensation reactions of salicylaldehyde, 2-pyridinecarboxaldehyde, and pyridoxaldehyde with memantine.
- Computational prediction of speciation, Log P, Log D, and neutral species percentage.
- Solubility determination in n-octanol.
- Hydrolysis studies of the synthesized Schiff bases.
Main Results:
- Three novel memantine-derived Schiff bases (1-3) were synthesized.
- Schiff bases exhibited increased lipophilicity (higher Log P and Log D) compared to memantine.
- Compound 3 showed high solubility and potential for transdermal delivery, releasing pyridoxal upon hydrolysis.
- Compound 3 is identified as the most promising candidate.
Conclusions:
- Memantine-derived Schiff bases enhance lipophilicity, suitable for transdermal delivery.
- Compound 3 represents a viable prodrug strategy for improved passive diffusion across biological barriers.
- This approach may offer therapeutic benefits for Alzheimer's disease and other neurological conditions.
Related Concept Videos
01:26Neurochemical Transmission: Sites of Drug Action
2.7K
Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...
2.7K
01:17Sedatives and Hypnotics Drugs: Miscellaneous Agents
254
Sedatives and hypnotics encompass a wide range of substances, each with its unique mechanism of action, uses, and potential adverse effects.
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
254
01:11Nondepolarizing (Competitive) Neuromuscular Blockers: Pharmacokinetics
548
All neuromuscular blocking agents are injected intravenously because they are poorly absorbed from the GI tract. Rapid onset is achieved with intravenous administration, although absorption is also adequate from an intramuscular injection. Since these agents are highly ionized, they do not readily penetrate cell membranes or cross the blood-brain barrier.
Instead, they are transported by the blood to different tissues. Muscles with a greater blood supply (arteries) and blood flow receive more...
Instead, they are transported by the blood to different tissues. Muscles with a greater blood supply (arteries) and blood flow receive more...
548
01:24Cholinergic Antagonists: Pharmacokinetics
572
Cholinergic antagonists—such as antimuscarinics—are available in oral, topical, ocular, parenteral, and inhalational formulations. Most antimuscarinics are oral formulations, while scopolamine is available as a topical patch, and ipratropium and tiotropium are available as inhalation aerosols or powders. Atropine, tropicamide, and cyclopentolate are topically instilled in the eye. Most antimuscarinics are lipid-soluble and readily absorbed from the gastrointestinal tract and...
572
01:22Drug Delivery: Miscellaneous Routes
495
Drug delivery methods like oral inhalation, nasal sprays, transdermal patches, eye drops, intravitreal injection, and rectal administration provide localized effects with reduced toxicity.
Oral inhalation and nasal sprays swiftly transfer drugs across the respiratory epithelium's mucosal layer. Inhaled glucocorticoids and bronchodilators directly target lung conditions such as asthma, while fluticasone nasal spray mitigates allergic rhinitis.
Transdermal patches transport drugs...
Oral inhalation and nasal sprays swiftly transfer drugs across the respiratory epithelium's mucosal layer. Inhaled glucocorticoids and bronchodilators directly target lung conditions such as asthma, while fluticasone nasal spray mitigates allergic rhinitis.
Transdermal patches transport drugs...
495
01:14Antiepileptic Drugs: Glutamate Antagonists
544
Glutamate is a fundamental neurotransmitter in the central nervous system, playing a vital role in neuronal communication and various cognitive processes. Glutamate stands as the principal excitatory neurotransmitter in the brain. Its presence is crucial for the communication between neurons, underpinning essential processes such as synaptic transmission, neuronal excitability, and plasticity. These functions are vital for higher-order cognitive processes, including learning and memory. The...
544